Abstract: Peripheral interleukin-1β (IL-β) and inflammatory stimuli that induce the synthesis and release of IL-1β produce a variety of central nervous system responses. Most proposals designed to explain how peripheral IL-1β influences the CNS have focused on blood-borne routes of communication. We will review data that indicate that at least some of the CNS response to peripheral IL-1β are instead mediated by a neural route of communication between the periphery and the CNS. IL-1β activates afferent vagal fibers that terminate in the nucleus tractus solitarius, and communication via the vagus is responsible for much of the hyperalgesia, fever, anorexia, taste aversions, increased levels of plasma corticosteroid, and brain norepinephrine changes produced by intraperitoneal injections of IL-1β and LPS. Data extending this analysis to TNF-α and intravenous routes will be described.